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Purpose: A leachable cyclic amide (caprolactam) can be found in normal saline (NS) and 5% dextrose in water (D5W) plastic bags widely used in clinical practice if they contain polyamide in a multilayer sheeting. This contamination and the parameters that could influence its content have never been studied in a public work such as a scientific publication., Methods: Two independent laboratories validated a caprolactam dosing method and studied contamination levels in several containers., Results: Caprolactam content in multilayer polypropylene/polyamide/polypropylene plastic bags ranged from a mean (SD) of 5.43 (0.21) mg/L (D5W 1,000 mL) to 22.83 (1.26) mg/L (NS 50 mL). NS and D5W can be intravenously administered with a total daily dose of 3 L, corresponding to a minimal daily dose of 16.3 mg of caprolactam., Conclusion: The high levels of contamination we have reported and the possibility of administering caprolactam to high-risk patients (eg, neonates, the elderly) should make it imperative for pharmaceutical companies to communicate publicly on the safety of caprolactam., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Parenteral N-acetylcysteine has a wide variety of clinical applications, but its use can be limited by a poor chemical stability. We managed to control parenteral N-acetylcysteine stability, and to study the influence of additives on the decrease of N-acetylcysteine degradation. First, an HPLC-UV dosing method of N-acetylcysteine and its main degradation product, a dimer, was validated and the stability without additive was studied. Then, the influence of several additives (ascorbic acid, sodium edetate, tocopherol and zinc) and of temperature on N-acetylcysteine dimerization was evaluated. Finally, the influence of zinc gluconate at different concentrations (administrable to patients) was investigated. Zinc gluconate at 62.5 µg·mL -1 allows the stabilization of 25 mg·mL -1 N-acetylcysteine solution for at least 8 days when stored at 5 ± 3 °C.

Background: Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D). We hypothesized that empaglifozin (EMPA) could modulate ectopic fat stores and myocardial energetics in high-fat-high-sucrose (HFHS) diet mice and in type 2 diabetics (T2D)., Methods: C57BL/6 HFHS mice (n = 24) and T2D subjects (n = 56) were randomly assigned to 12 weeks of treatment with EMPA (30 mg/kg in mice, 10 mg/day in humans) or with placebo. A 4.7 T or 3 T MRI with 1 H-MRS evaluation-myocardial fat (primary endpoint) and liver fat content (LFC)-were performed at baseline and at 12 weeks. In humans, standard cardiac MRI was coupled with myocardial energetics (PCr/ATP) measured with 31 P-MRS. Subcutaneous (SAT) abdominal, visceral (VAT), epicardial and pancreatic fat were also evaluated. The primary efficacy endpoint was the change in epicardial fat volume between EMPA and placebo from baseline to 12 weeks. Secondary endpoints were the differences in PCr/ATP ratio, myocardial, liver and pancreatic fat content, SAT and VAT between groups at 12 weeks., Results: In mice fed HFHS, EMPA significantly improved glucose tolerance and increased blood ketone bodies (KB) and β-hydroxybutyrate levels (p < 0.05) compared to placebo. Mice fed HFHS had increased myocardial and liver fat content compared to standard diet mice. EMPA significantly attenuated liver fat content by 55%, (p < 0.001) but had no effect on myocardial fat. In the human study, all the 56 patients had normal LV function with mean LVEF = 63.4 ± 7.9%. Compared to placebo, T2D patients treated with EMPA significantly lost weight (- 2.6 kg [- 1.2; - 3.7]) and improved their HbA1c by 0.88 ± 0.74%. Hematocrit and EPO levels were significantly increased in the EMPA group compared to placebo (p < 0.0001, p = 0.041). EMPA significantly increased glycosuria and plasma KB levels compared to placebo (p < 0.0001, p = 0.012, respectively), and significantly reduced liver fat content (- 27 ± 23 vs. - 2 ± 24%, p = 0.0005) and visceral fat (- 7.8% [- 15.3; - 5.6] vs. - 0.1% [- 1.1;6.5], p = 0.043), but had no effect on myocardial or epicardial fat. At 12 weeks, no significant change was observed in the myocardial PCr/ATP (p = 0.57 between groups)., Conclusions: EMPA effectively reduced liver fat in mice and humans without changing epicardial, myocardial fat or myocardial energetics, rebutting the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors. Trial registration NCT, NCT03118336. Registered 18 April 2017, https://clinicaltrials.gov/ct2/show/NCT03118336.

Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d -1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically ( P < 0.01), with no deaths, significant decreases in oxygen requirements ( P < 0.05), and more days without invasive mechanical ventilation ( P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and multiorgan failure, resulting from autoantibody-mediated severe A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) deficiency. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk of exacerbations, refractoriness and death. Caplacizumab (Cablivi; Ablynx, a Sanofi company), a nanobody targeting von Willebrand factor (vWF), has been recently approved in the E.U. and the U.S. as the first therapeutic specifically indicated for the treatment of adults experiencing an episode of iTTP. Caplacizumab blocks the interaction of all multimers with platelets and, therefore, has an immediate effect on platelet aggregation and the ensuing formation and accumulation of platelet-rich microthrombi. This immediate effect of caplacizumab has the potential to protect the patient from tissue ischemia and organ dysfunction while the underlying disease process resolves. We detail here the preclinical and clinical data on caplacizumab for iTTP, including the recent studies that led to approval by the U.S. Food and Drug Administration (FDA) in 2019., (Copyright 2019 Clarivate Analytics.)

In intensive care, beta-lactams can be reconstituted in 50 mL polypropylene syringes with NaCl 0.9 % and administered for 8 to 12 h at various concentrations with motor-operated syringe pumps. The feasibility and/or the stability of these antibiotic therapies are often poorly known by clinicians. The purpose of this study was to determine the stability of seven antipyocyanic beta-lactam antibiotics and cilastatin under real-life conditions. Stability indicating HPLC methods allowing quantification in pharmaceutical preparations and subsequent stability studies were performed. The stability studies showed that continuous infusion of piperacillin/tazobactam 80/10 mg/mL, of cefepime 20 and 40 mg/mL and of aztreonam 40 and 120 mg/mL can be used over 12 h. Moreover, continuous infusion of cefepime 120 mg/mL can be used over 10 h, whereas meropenem 10 and 20 mg/mL and ceftazidime 40 mg/mL remained stable only over 8 h, and meropenem 40 mg/mL was significantly degraded after 6 h. Finally, imipenem/cilastatin 5/5 mg/mL and piperacillin/tazobactam 320/40 mg/mL should not be used as continuous infusion. These data allow the establishment of protocols of administration of antipyocyanic beta-lactams by continuous infusion. Some of them are not appropriate to this mode of administration (imipenem/cilastatin, piperacillin/ tazobactam 320/40 mg/mL) or must be avoided if possible (ceftazidime 40 mg/mL).

Despite its benign characteristics, chickenpox is a childhood disease responsible for complications and deaths, particularly in the high-risk population. VariZIG ® , not commercialized in France, is a good alternative for seronegative individuals exposed to the virus and not eligible for vaccination. The efficacy of routine vaccination has been demonstrated with a decrease in chickenpox incidence and with the development of herd immunity. Over time, the protective antibody titer of vaccinated people decreases and can be maintained by two doses of the vaccine. A tetravalent measles-mumps-rubella-chickenpox vaccine, used in the United States, has a good tolerability in spite of the occurrence of fever and febrile seizures. Routine vaccination would contribute to make savings in France, by reducing direct and indirect costs of chickenpox., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole.

The observed increase in cancer led to a continuous rise in anticancer drug preparations in Hospital Centres. The quality and security of these preparations are essential to ensure the efficacy and to limit the risk of iatrogenic toxicity. Several methods have been described to secure the process of preparation (i.e. non-analytical methods for the control during the fabrication; analytical methods for the final product evaluation). These different methods have been presented in many studies, in particular in descriptive studies, but in practice, selecting a method is difficult and related to needs and hospital priorities. Therefore, we decided to conduct this present review focused on various existing methods allowing enhancement in security of anti-cancer drugs preparation process. A proactive hazard analysis method was applied, considering preparation and control steps, to discuss the choice of a method in terms of quality and security and to identify potential risks of failure. The results show that none method is perfect. Methods with the lowest criticality score are the robotization closely followed by Drugcam® in the case of re-labelling of all containers. According to these elements a University Hospital Centre could consider these risk indexesimplementing control methods.

In 2015, the World Health Organization registered 10.4 million people who developed tuberculosis worldwide and 480,000 new cases of multidrug-resistant tuberculosis were identified. The care of multi and extensively drug-resistant tuberculosis is based on a combination of pyrazinamide and second-line drugs. These regimens are lengthy, partially effective and poorly tolerated. The challenge is to re-evaluate the use of existing molecules and to develop new agents more effective against resistant strains with shorter treatment duration. This literature review gives an overview of the latest research addressing these therapeutic objectives. Some molecules are in late stage clinical development among which pretomanid is showing promising results. Bedaquiline and delamanid have been recently approved by the Food and Drug Administration. The efficacy of drug regimens combining these molecules is under evaluation.

Some antibiotics are reserved essentially for hospital settings owing to cost effectiveness and in order to fight the emerging antibiotic resistance crisis. In some cases, antibiotics reserved exclusively for use in hospitals may be prescribed in outpatients for serious infections or in the absence of a therapeutic alternative. A 30-day prospective audit of outpatient prescriptions of antibiotics reserved exclusively for use in hospitals was performed. The objective of this study was to evaluate the relevance of outpatient antibiotic prescriptions by measuring appropriateness according to guidelines. During the study period, 53 prescriptions were included, only 40% of which were appropriate. Among the 32 inappropriate prescriptions, 4 cases lacked microbial arguments, 1 case was not adequate for the infection type, 1 case involved an incorrect antibiotic dosage, 1 case involved an incorrect interval of dose administration, 3 cases had a therapeutic alternative and 22 cases were not recommended. Of the 53 prescriptions, 66% were started in hospital and 34% in outpatients. Only 25% of cases were prescribed with infectious diseases specialist (IDS) advice, 64% were based on microbiological documentation and 13% had a negative bacterial culture. Inappropriate prescriptions were usually observed in antibiotic lock therapy, skin infections, Clostridium difficile colitis, intra-abdominal infections and intravascular catheter-related infections. Outpatient prescriptions of antimicrobial drugs reserved exclusively for use in hospitals are frequently inappropriate. We recommend a real-time analysis algorithm with the involvement of an IDS for monitoring prescriptions to improve the quality of these prescriptions and possibly to prevent antibiotic resistance., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: A Tat Oyi vaccine preparation was administered with informed consent to 48 long-term HIV-1 infected volunteers whose viral loads had been suppressed by antiretroviral therapy (cART). These volunteers were randomized in double-blind method into four groups (n = 12) that were injected intradermally with 0, 11, 33, or 99 µg of synthetic Tat Oyi proteins in buffer without adjuvant at times designated by month 0 (M0), M1 and M2, respectively. The volunteers then underwent a structured treatment interruption between M5 and M7., Results: The primary outcomes of this phase I/IIa clinical trial were the safety and lowering the extent of HIV RNA rebound after cART interruption. Only one undesirable event possibly due to vaccination was observed. The 33 µg dose was most effective at lowering the extent of HIV RNA and DNA rebound (Mann and Whitney test, p = 0.07 and p = 0.001). Immune responses against Tat were increased at M5 and this correlated with a low HIV RNA rebound at M6 (p = 0.01)., Conclusion: This study suggests in vivo that extracellular Tat activates and protects HIV infected cells. The Tat Oyi vaccine in association with cART may provide an efficient means of controlling the HIV-infected cell reservoir.

Neisseria meningitidis infections are a major public health problem worldwide. Although conventional approaches have not led to development of a serogroup B meningococcal vaccine, a new technique based on genome sequencing has created new perspectives. Recently, a universal serogroup B meningococcal vaccine, Bexsero(®), was licensed in Europe, Australia and United States, following several clinical studies demonstrating its immunogenicity and safety. Availability of this vaccine could contribute positively to human health, by significantly reducing the incidence of meningococcal infections. However, unfavorable cost-effectiveness analysis means that routine vaccination is not currently recommended. Another serogroup meningococcal vaccine, Trumemba(®), was also recently licensed in United States. Like any drug, Bexsero(®) and Trumemba(®) will require close observation to assess their impact on meningococcal epidemiology., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Hemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: Exposure to sunlight is one of the environmental factors involved in the pathogenesis of systemic lupus erythematosus. We investigated whether there is seasonal variation in the incidence of cutaneous and noncutaneous severe lupus flares in southern France., Methods: We retrospectively reviewed clinical and biological data from all SLE patients hospitalized for a flare of the disease during a two year period in our centre and collected corresponding meteorological data from the official website of MeteoFrance., Results: Forty one patients, mean age 36.7 ± 13.8 years, were included. Twenty-six patients (63.4%) had kidney biopsy performed, showing in all cases proliferative nephritis, associated with membranous nephritis in 9 (22%). We found a clear seasonal pattern for overall lupus flares with 39% of flares occurred in Spring. Among patients without any cutaneous involvement, this seasonal pattern was still observed (p=0.024). Patients under antimalarials presented flares significantly later in the sunny season than those without (respectively median in July versus May, p=0.044). There were strong positive correlations between occurrence of lupus flares and maximum temperature increase (ρ=0.87, p<0.001), minimum temperature increase (ρ=0.87, p<0.001), and duration of sunshine increase (ρ=0.78, p=0.003). These correlations were also observed in patients with renal flares., Conclusion: We confirmed a seasonal pattern for lupus flares among patients living in Southern France, with most flares in spring, in correlation with an increase in temperature and duration of sunshine. A similar seasonal pattern was observed in patients with no cutaneous involvement and with visceral involvement., (Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

We conducted a retrospective survey to assess prescription practice, response rates to rituximab, and the predictive indicators for a response to rituximab therapy in patients with primary or secondary immune thrombocytopenic purpura (ITP). Data were collected retrospectively from 40 consecutive patients with ITP attending our hospital: 29 (72.5%) had primary ITP and 11 (27.5%) had secondary ITP. Rituximab was given either as four weekly injections (375 mg/m(2)) or two injections of 1,000 mg given 2 weeks apart in 30 and 10 patients, respectively. The primary objective was to evaluate overall (OR) and complete response (CR) to rituximab therapy for ITP. OR was excellent and rapid and similar when secondary ITP was excluded from the analysis: OR was achieved in 28 (71.8%) patients and CR in 22 (56.4%). But, at >6 months, of the 28 responders, only 10 of 22 of the evaluable responses (45.5%) were sustained. In addition, except for the nonsignificant occurrence of antinuclear antibodies, no clinical or biological factors were predictive for OR or CR after the rituximab therapy. Twelve patients received a second course of rituximab. Overall, rituximab therapy achieved a response in two thirds of the patients, but the responders exhibited a high rate of early relapses, with no obvious difference according to the regimen of administration or rituximab dose.

Belimumab is the first biologic approved for patients with systemic lupus erythematosus (SLE). Belimumab is the first of a new class of drug targeting B cell-stimulating factors or their receptors to reach the market. Its target, BLyS, also known as BAFF (B cell-activating factor from the tumor necrosis factor family), is a type II transmembrane protein that exists in both membrane-bound and soluble forms. Additionally to a robust rational from murine experiments conducted in lupus prone mice, BLyS circulating levels are increased in SLE patients. After the negative results of a Phase II trial, two Phase III trials met their primary endpoints. Some SLE patients are still refractory to the standard options of care or necessitate prolonged high-dose corticotherapy and/or long-term immunosuppressive regimens. However, some experts still feel that the effect of this biologic might not be clinically relevant and blame the use of the new systemic lupus response index as well as the discrepancies between both trials and the noninclusion of the severe form of the disease as nephritis. In this review, we aim to discuss the characteristics of belimumab, critically evaluate the different steps of its development, and consider its future place in the arsenal against SLE, taking into account the patients' perspectives.

Since several years, the use of intravenous immunoglobulins (IVIg) has increased. This growth has encouraged some countries to publish guidelines. In parallel, some countries have conducted audits to know how IVIg are used in clinical practice in the light of the available guidelines. The objective of this study was to assess IVIg use in three French university hospitals in 2006. All IVIg administrations were evaluated during 6 months (12 September 2005-12 March 2006) in French university hospitals of Marseille. Different data were recorded for each administration: patient characteristics, indication, formulation and quantity. During the study period, 2802 administrations of IVIg (corresponding to a total quantity of 76 780 g) have been recorded. Four hundred and thirty-five patients received at least one of these administrations. The five most reported indications were multifocal motor neuropathy (11.0% of total quantity), chronic inflammatory demyelinating polyradiculoneuropathy (10.2%), corticoresistant dermatomyositis (10.2%), immune thrombocytopaenia (9.9%) and primary immune deficiency (9.1%). According to available French recommendations, 70% of the IVIg use was for 'acknowledged indications', 9% for 'indications to be assessed' and 18% for 'unwarranted indications'. The 10 most reported indications were 'acknowledged indications' according to available recommendations of the French expert group. Nevertheless, the two most reported indications were not approved by the French Health Products Agency (AFSSAPS) at the time of the study and were approved since., (2011 The Authors Fundamental and Clinical Pharmacology. 2011 Société Française de Pharmacologie et de Thérapeutique.)

Introduction: Tramadol is a weak opioid analgesic used as a step two analgesic, approved in France for the treatment of moderate to severe pain in adult patients. The most common side effects are gastrointestinal and neurologic. Hypoglycaemia is an almost unknown side effect., Case Reports: We report two patients who presented with severe hypoglycaemia related to oral administration of tramadol in non diabetic patients. The underlying mechanisms of hypoglycaemia induced by tramadol are unclear. The only weak opioid analgesic drug reported to cause hypoglycaemia is propoxyphene, which has been widely used in France. The recent withdrawal of dextropropoxyphene in France might increase the prescriptions of tramadol and healthcare professionals should be aware of the risk of hypoglycaemia., Conclusion: The risk of hypoglycaemia should be added to the summary of product characteristics of tramadol., (Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

In Enterobacter aerogenes, beta-lactam resistance often involves a decrease in outer membrane permeability induced by modifications of porin synthesis. In ATCC 15038 strain, we observed a different pattern of porin production associated with a variable antibiotic susceptibility. We purified Omp35, which is expressed under conditions of low osmolality and analyzed its pore-forming properties in artificial membranes. This porin was found to be an OmpF-like protein with high conductance values. It showed a noticeably higher conductance compared to Omp36 and a specific location of WNYT residues in the L3 loop. The importance of the constriction region in the porin function suggests that this organization is involved in the level of susceptibility to negative large cephalosporins such as ceftriaxone by bacteria producing the Omp35 porin subfamily.

Enterobacter aerogenes develops increased multidrug resistance via a functional alteration of outer-membrane permeability associated with a decrease in porin function. We have sequenced the gene coding the major porin of Enterobacter aerogenes, omp36. The sequence shows a high similarity with the Klebsiella pneumoniae ompK36 gene and is closely related to the enterobacterial OmpC family. Sequence analysis of several Omp36 issued from clinical strains indicated variability in putative cell-surface exposed domains. Interestingly, substitution Gly112Asp was observed in the conserved eyelet L3 region of the porin produced by two strains, C and 3. This substitution is associated with a high general beta-lactam resistance observed in these isolates and with alteration of pore properties previously described in strain 3 porin [Mol. Microbiol. 41 (2001) 189]. This is the first genetic identification of impermeability-mediated resistance to beta-lactams in various clinical E. aerogenes strains.

Purpose: To study cataract formation in eyes with an implantable contact lens (ICL) used for moderate to high myopia., Setting: University Eye Hospital, Lausanne, Switzerland., Methods: An ICL (model V3 or V4, Staar Surgical AG) was implanted in 75 eyes. Three months after surgery and again at the last follow-up examination, the transparency of the crystalline lens was assessed on transilluminated photographs and the vaulting of the ICL over the crystalline lens was evaluated. Central vaulting was measured precisely on digitized photographs taken with a 75 SL Zeiss slitlamp camera, while peripheral vaulting was estimated on photographs obtained with a Scheimpflug camera. The minimum follow-up was 12 months; the mean was 21.8 months., Results: At the last follow-up, 20 of the 75 eyes (27%) had an ICL-induced anterior subcapsular cataract (ASCC). The number of cataracts increased with the duration of the follow-up. Cataracts developed more commonly in older patients than in younger patients. All 20 cataracts occurred when the central vaulting was equal to or less than 0.09 mm. In 26 eyes with the same range of vaulting (among which 11 had no vaulting), the lenses were clear at the last visit. The 20 patients with cataract and the 26 patients with clear lenses matched in age and duration of follow-up but not in myopia. No touch between the ICL and the crystalline lens was encountered when the central vaulting was equal to or greater than 0.15 mm. Vaulting showed a slight decrease over time. No statistically significant difference in vaulting was found between models V3 and V4., Conclusion: Central and/or peripheral contact between the ICL and the crystalline lens may be responsible for the high incidence of ASCC formation in this study. Central vaulting greater than 0.09 mm appears to protect the crystalline lens from cataract formation. However, we recommend aiming for higher central vaulting (0.15 mm) to avoid contact between the ICL and the crystalline lens. This should be attainable by implanting longer ICLs.

Imipenem is often used to treat intensive care unit patients infected by Enterobacter aerogenes, but it is leading to an increasing number of antibiotic resistant strains. Clinical isolates and imipenem resistant variants presented a high level of resistance to beta-lactam antibiotic group and to chemically unrelated drugs. We report here that imipenem selects strains which contain active efflux pumps ejecting various unrelated antibiotics including quinolones, tetracycline, and chloramphenicol. An increase of AcrA, an efflux pump component, was observed in the imipenem resistant variants. The overexpression of marA, involved in the genetic control of membrane permeability via porin and efflux pump expression, indicated the activation of the resistance genetic cascade in imipenem resistant variants.

Purpose: To confirm the safety, efficacy, and predictability of the surgical correction of moderate to high myopia by the ICM V3 and ICM V4 implantable contact lenses (ICLs), with emphasis on vaulting, intraocular pressure (IOP), and pigment dispersion., Setting: University Eye Hospital, Lausanne, Switzerland., Methods: Thirty-two eyes had implantation of an ICL. In 22 eyes with a mean spherical equivalent (SE) of -11.5 diopters (D), the target was emmetropia; in 10 eyes with a mean SE of -22.3 D, the goal was a reduction in the myopia. Nineteen eyes received the ICM V3 ICL and 13, the ICM V4 ICL. The mean follow-up was 7.4 months., Results: The mean postoperative SE in the 32 eyes was -2.16 D. Best spectacle-corrected visual acuity was maintained or improved in all eyes. In the 22 eyes targeted to achieve emmetropia, 10 (45%) were within +/-1.00 D; 15 (68%) had an uncorrected visual acuity of 20/40 or better and 4 (18%), of 20/20 or better. Vaulting of the ICL over the crystalline lens was more pronounced with the V4 than with the V3, and the difference was statistically significant. Subtle, localized anterior subcapsular opacification was encountered in 4 eyes. In 3 of them, the ICL (model V3) vaulting was minimal and 1 ICL (model V4) did not show any vaulting. Eighteen eyes had an IOP higher than the preoperative level, and the difference was statistically significant. No correlation was seen between final IOP and vaulting. Pigment dispersion on the ICL did not appear to be related to vaulting or ICL thickness., Conclusion: Implantation of an ICL was effective in correcting moderate to high myopia of up to -17.50 D. Although the procedure appears to be safe, the predictability of the refractive outcome must be improved. The new generation of ICLs for myopia (ICM V4) offers a better vault over the crystalline lens than the older models (ICM V3), which should decrease the risk of cataract. No explanation was found for the IOP increase in several eyes 3 months or more after surgery.

Purpose: To define the clinical outcome and microbiological pattern of bacterial endophthalmitis that were referred at the Jules Gonin Eye Hospital from January 1997 to September 1999., Methods: Patients were recorded in a computerised databank and were managed according to a standard protocol. An anterior chamber tap combined with a vitreous biopsy by the pars plana was performed in all patients. The treatment included an intravitreal injection of 1 mg Vancomycin and 400 micrograms Amikacin diluted in 0.2 ml NaCl 0.9%. Postoperatively hourly therapy Cefazolin 50 mg/ml and Garamycin 9 mg/ml was applied. To determine possible risks factors a standard form was sent to all referring surgeons. The following data were analysed: delay of onset, risk factors, initial and final visual acuity., Results: From January 1997 to September 1999, 31 patients were referred. 18/31 (58%) of the cases were admitted between April and June of each years. The mean age was of 75 +/- 10 years. Initial visual acuity ranged from light perception to 20/40. 17/31 of the patient's cultures were positive. The major pathogen were Staphylococcus epidermidis in 9/31 patients and Staphylococcus aureus in 4/31 patients. No correlation between the endophthalmitis and the surgical technique or perioperative management of the patient, could be determined. Visual outcome was significantly improved in 56.7% of the patients., Conclusions: The severity of outcome could be correlated to the type of bacteria isolated. The high prevalence of panophthalmitis from March to June suggests that a climatic factors may be involved in its pathogenesis.

Multidrug-resistant Enterobacter aerogenes strains are increasingly isolated in Europe and especially in France. Treatment leads to imipenem resistance, because of a lack of porin. We studied the evolution of resistance in 29 strains isolated from four patients during their clinical course. These strains belonged to the prevalent epidemiological type observed in France in previous studies (C. Bosi, et al., J. Clin. Microbiol. 37:2165-2169, 1999; A. Davin-Regli et al., J. Clin. Microbiol. 34:1474-1480, 1996). They also harbored a TEM-24 extended-spectrum beta-lactamase-coding gene. Thirteen strains were susceptible to gentamicin and resistant to imipenem and cefepime. All of the patients showed E. aerogenes strains with this resistance after an imipenem treatment. One patient showed resistance to imipenem after a treatment with cefpirome. Twelve of these 13 strains showed a lack of porin. Cessation of treatment with imipenem for three patients was followed by reversion of susceptibility to this antibiotic and the reappearance of porins, except in one case. For one patient, we observed three times in the same day the coexistence of resistant strains lacking porin and susceptible strains possessing porin. The emergence of multidrug-resistant E. aerogenes strains is very disquieting. In our study, infection by E. aerogenes increased the severity of the patients' illnesses, causing a 100% fatality rate.

The aim of this study was to determine the distribution in France of the Enterobacter aerogenes prevalent clone isolated in the hospitals of the Marseille area (A. Davin-Regli, D. Monnet, P. Saux, C. Bosi, R. Charrel, A. Barthelemy, and C. Bollet, J. Clin. Microbiol. 34:1474-1480, 1996). A total of 123 E. aerogenes isolates were collected from 23 hospital laboratories and analyzed by random amplification of polymorphic DNA and enterobacterial repetitive intergenic consensus-PCR to determine their epidemiological relatedness. Molecular typing revealed that 21 of the 23 laboratories had isolated this prevalent clone harboring the plasmid encoding for extended-spectrum beta-lactamase of the TEM-24 type. Most isolates were susceptible only to imipenem and gentamicin. Their dissemination seems to be clonal and was probably the result of the general use of broad-spectrum cephalosporins and quinolones. Four isolates showed an alteration of their outer membrane proteins, causing decrease of susceptibility to third-generation cephalosporins and imipenem and leading to the critical situation of having no alternative therapeutic. The large dissemination of the E. aerogenes prevalent clone probably results from its good adaptation to the antibiotics administered in France and the hospital environment, particularly in intensive care units.

The exact composition of calculi is clinically important, but many specimens are not examined, with resultant loss of important information. We describe the incidence and nature of false stones, peculiar calculi and crystals growing on surprising materials. We studied 3100 calculi (97% urinary, 2% digestive and 1% others). Fourier transform infrared spectroscopy was used to identify calculi by detailed comparison with libraries of reference spectra. We also used UV-visible spectroscopy, nuclear magnetic resonance and gas chromatography-mass spectrometry for specific situations. Among 3100 calculi, 154 (5%) had an unusual composition; 101 specimens (3.3%) were false calculi or artifacts, 31 (1%) contained drugs or metabolites and 22 (0.7%) corresponded to crystallizations around other materials. The findings contribute to immediate patient management and to advances in scientific and medical knowledge. We conclude that the analysis of all calculi must be carried out, to determine their composition, and an efficient strategy must be used.

Enterobacter aerogenes is among the five most frequently isolated nosocomial pathogens in France, and this bacterium also shows increasing multidrug resistance. In this study, various E. aerogenes strains isolated from hospital units were characterized for their outer-membrane proteins, antibiotic susceptibilities (inhibition diameters and MICs) and resistance mechanisms associated with modification of envelope permeability (porin alteration and active efflux). Diminished outer-membrane permeability due to porin alterations was found in conjunction with the expression of an enzymic barrier in resistant isolates. Interestingly, changes in the functional expression of porins appeared to play a special role in susceptibility to cefepime. An active efflux to quinolones was also identified. Simultaneous changes in envelope permeability, i.e. a porin deficiency (in) and an efflux mechanism (out), were clearly evident in two clinical strains.